This project focuses on the function of immune response (Ir) genes in the activation of thymus-derived (T)-lymphocytes using radiation-induced bone marrow chimeras, a secondary T cell proliferation assay, and a newly developed technique for cloning antigen-specific T lymphocytes. With the chimeras we have been able to generate evidence which suggests that Ir gene products are the serologically detectable Ia antigens which function primarily in macrophages of both the thymus and peripheral tissues and are involved in the presentation of antigen. Using the cloning technique we have demonstrated major histocompatibility complex (MHC) restriction at the level of a single cell and its progenitors proving that allogeneic suppression cannot explain the requirement of T-cells to see antigen in association with with self MHC products. Finally, studies of the proliferative response to the antigen, pigeon cytochrome C, demonstrated that two complementing Ir genes could control the response to a single antigenic determinant and that both gene products must be present in the same antigen-presenting cell in order to stimulate a response.